Silencing of FUS in the common marmoset (Callithrix jacchus) brain via stereotaxic injection of an adeno-associated virus encoding shRNA

• Published in: Neuroscience research 2018-05, Vol.130, p.56-64
• Main Authors: Endo, Kuniyuki, Ishigaki, Shinsuke, Masamizu, Yoshito, Fujioka, Yusuke, Watakabe, Akiya, Yamamori, Tetsuo, Hatanaka, Nobuhiko, Nambu, Atsushi, Okado, Haruo, Katsuno, Masahisa, Watanabe, Hirohisa, Matsuzaki, Masanori, Sobue, Gen
• Format: Article
• Language: English
• Subjects: Adenoviridae - physiology; Animals; Brain - metabolism; Callithrix; Common marmoset; Disease Models, Animal; Female; Frontotemporal lobar degeneration; Frontotemporal Lobar Degeneration - genetics; FUS; Genetic Vectors - administration & dosage; HEK293 Cells; Humans; Neurons - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-Binding Protein FUS - antagonists & inhibitors; RNA-Binding Protein FUS - genetics; Stereotaxic Techniques
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2017.08.006

•The common marmoset FUS coding sequence was identified.•An AAV vector system for silencing FUS expression in the brain of the common marmoset was developed.•An immunological response provoked following FUS suppression was observed. Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side. We obtained approximately 70–80% silencing of FUS following AAV-shFUS injection. Interestingly, FUS-silencing provoked a proliferation of astrocytes and microglias. Since FTLD is characterized by various emotional deficits, it would be helpful to establish a marmoset model of FUS-silencing in various brain tissues for investigating the pathomechanism of higher cognitive and behavioral dysfunction.